The principal goal of this proposal remains the identification of peptides, isolated from rat hypothalamic tissue which influence secretion from the endocrine pancreas. We will concentrate on completing the analysis of two glucagon releasing peptides which we have purified by ultrafiltration, gel-ion exchange and high pressure liquid chromatography and partially characterized by compositional and sequential analysis. Availability of synthetic peptide(s) and specific antisera will then permit evaluation of physiological function which at present is envisaged in the form of a neuroendocrine or neuromodulatory, agent which participates in the contribution of the CNS to glucose mobilization via glucagon in response to the demands of stress and insulin counterregulating situations. Malfunctions in this system could well contribute to the development of diabetic, obese or anorexic conditions in the human. We also intend to use HPLC and immunoassays to determine whether the hypothalamic insulin release-inhibiting factor which we partially purified some years ago, resembles corticotropin releasing factor or B-endorphin as they show similar gel-filtration behavior and each has been found to inhibit release of insulin. In parallel experiments we will examine pancreatic extracts by HPLC for the presence of A and B cell-regulating peptides corresponding to those found in brain tissue while ascertaining that the corticotropin releasing factor-, oxytocin- and vasopressin-like immunoactive species which we have recently found in pancreatic extracts are in fact peptides identical to their hypothalamic or neurohypophysial counterparts.